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Cited by 382Iron Metabolism and DisordersRNA Research and SplicingPlant Micronutrient Interactions and Effects

Coordinated Remodeling of Cellular Metabolism during Iron Deficiency through Targeted mRNA Degradation

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Puig, Sergi, Askeland, Eric, Thiele, Dennis J.·2005·Cell
DOI 10.1016/j.cell.2004.11.032
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Abstract

Iron (Fe) is an essential micronutrient for virtually all organisms and serves as a cofactor for a wide variety of vital cellular processes. Although Fe deficiency is the primary nutritional disorder in the world, cellular responses to Fe deprivation are poorly understood. We have discovered a posttranscriptional regulatory process controlled by Fe deficiency, which coordinately drives widespread metabolic reprogramming. We demonstrate that, in response to Fe deficiency, the Saccharomyces cerevisiae Cth2 protein specifically downregulates mRNAs encoding proteins that participate in many Fe-dependent processes. mRNA turnover requires the binding of Cth2, an RNA binding protein conserved in plants and mammals, to specific AU-rich elements in the 3' untranslated region of mRNAs targeted for degradation. These studies elucidate coordinated global metabolic reprogramming in response to Fe deficiency and identify a mechanism for achieving this by targeting specific mRNA molecules for degradation, thereby facilitating the utilization of limited cellular Fe levels.

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  • S. cerevisiae Cth2, along with its paralog Cth1, targets mRNA of iron-dependent genes for degradation via binding to this motif.

    “S. cerevisiae Cth2 (ScCth2), along with its paralog Cth1, was found specifically to target mRNA of iron-dependent genes for degradation via binding to this motif (22, 24), whereas the corresponding Cth2 protein in C. glabrata was still uncharacterized.”

    From A novel hybrid iron regulation network combines features from pathogenic and nonpathogenic yeasts (2016) · cites this paper as [24]

  • In S. cerevisiae, the Aft1 regulon recruits the mRNA-degrading protein Cth2, which posttranscriptionally reduces the abundance of iron consumption-related mRNAs under conditions of iron deprivation.

    “In S. cerevisiae, the Aft1 regulon is known to recruit the mRNA-degrading protein Cth2 (also known as Tis11), which posttranscriptionally reduces the abundance of iron consumption-related mRNAs under conditions of iron deprivation (22, 24).”

    From A novel hybrid iron regulation network combines features from pathogenic and nonpathogenic yeasts (2016) · cites this paper as [24]

  • In both C. glabrata and S. cerevisiae, Cth2 target transcripts code especially for proteins with a role in iron consumption.

    “In both species, these are transcripts coding especially for proteins with a role in iron consumption (24).”

    From A novel hybrid iron regulation network combines features from pathogenic and nonpathogenic yeasts (2016) · cites this paper as [24]

  • The mode of recognition by Cth2 is evolutionarily conserved between C. glabrata and S. cerevisiae, with a large set of overlapping target genes, while the sets of regulated target genes differ greatly between all other investigated species.

    “These observations indicate a mode of recognition by Cth2 that is evolutionarily conserved between C. glabrata and S. cerevisiae, with a large set of overlapping target genes (24), while the sets of regulated target genes differ greatly between all other investigated species.”

    From A novel hybrid iron regulation network combines features from pathogenic and nonpathogenic yeasts (2016) · cites this paper as [24]

  • In contrast to S. cerevisiae, the Cth2-binding motif is present in FTR1, FET3, and SIT1 transcripts in C. glabrata.

    “In contrast to S. cerevisiae (24), the Cth2-binding motif is present in FTR1, FET3, and SIT1 transcripts”

    From A novel hybrid iron regulation network combines features from pathogenic and nonpathogenic yeasts (2016) · cites this paper as [24]

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Authors
Puig, S., Askeland, E., & Thiele, D. J.
Affiliations
Duke University (US)
Corresponding author
Thiele, Dennis J.
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2005-01
Volume
120
Issue
1
Pages
99-110
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2004.11.032
OpenAlex
W1991379214
Cited by
382
References
38
Citations by year
2026: 2 · 2025: 10 · 2024: 10 · 2023: 7 · 2022: 16 · 2021: 20 · 2020: 15 · 2019: 9 · 2018: 21 · 2017: 26 · 2016: 19 · 2015: 11 · 2014: 21 · 2013: 21 · 2012: 29
FWCI
17.72
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institutes of Health
Topics
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Micronutrient Interactions and Effects
Keywords
iron deficiency, cellular metabolism, mRNA degradation, AU-rich elements, RNA-binding proteins, post-transcriptional regulation, metabolic reprogramming, 3' untranslated region, Saccharomyces cerevisiae
MeSH terms
Base Sequence, DNA-Binding Proteins, Iron, Molecular Sequence Data, Mutation, Plasmids, RNA Processing, Post-Transcriptional, RNA, Messenger, Saccharomyces cerevisiae, Transcription, Genetic, Down-Regulation, Gene Expression Regulation, Fungal, Saccharomyces cerevisiae Proteins, Tristetraprolin

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